254 research outputs found

    Identification of foot pathologies based on plantar pressure asymmetry

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    Foot pathologies can negatively influence foot function, consequently impairing gait during daily activity, and severely impacting an individual’s quality of life. These pathologies are often painful and correspond with high or abnormal plantar pressure, which can result in asymmetry in the pressure distribution between the two feet. There is currently no general consensus on the presence of asymmetry in able-bodied gait, and plantar pressure analysis during gait is in dire need of a standardized method to quantify asymmetry. This paper investigates the use of plantar pressure asymmetry for pathological gait diagnosis. The results of this study involving plantar pressure analysis in fifty one participants (31 healthy and 20 with foot pathologies) support the presence of plantar pressure asymmetry in normal gait. A higher level of asymmetry was detected at the majority of the regions in the feet of the pathological population, including statistically significant differences in the plantar pressure asymmetry in two regions of the foot, metatarsophalangeal joint 3 (MPJ3) and the lateral heel. Quantification of plantar pressure asymmetry may prove to be useful for the identification and diagnosis of various foot pathologies

    Experimental and Computational Analysis of Polyglutamine-Mediated Cytotoxicity

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    Expanded polyglutamine (polyQ) proteins are known to be the causative agents of a number of human neurodegenerative diseases but the molecular basis of their cytoxicity is still poorly understood. PolyQ tracts may impede the activity of the proteasome, and evidence from single cell imaging suggests that the sequestration of polyQ into inclusion bodies can reduce the proteasomal burden and promote cell survival, at least in the short term. The presence of misfolded protein also leads to activation of stress kinases such as p38MAPK, which can be cytotoxic. The relationships of these systems are not well understood. We have used fluorescent reporter systems imaged in living cells, and stochastic computer modeling to explore the relationships of polyQ, p38MAPK activation, generation of reactive oxygen species (ROS), proteasome inhibition, and inclusion body formation. In cells expressing a polyQ protein inclusion, body formation was preceded by proteasome inhibition but cytotoxicity was greatly reduced by administration of a p38MAPK inhibitor. Computer simulations suggested that without the generation of ROS, the proteasome inhibition and activation of p38MAPK would have significantly reduced toxicity. Our data suggest a vicious cycle of stress kinase activation and proteasome inhibition that is ultimately lethal to cells. There was close agreement between experimental data and the predictions of a stochastic computer model, supporting a central role for proteasome inhibition and p38MAPK activation in inclusion body formation and ROS-mediated cell death

    Thrombin responses in human endothelial cells. Contributions from receptors other than PAR1 include the transactivation of PAR2 by thrombin-cleaved PAR1.

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    The recent identification of two new thrombin receptors, PAR3 and PAR4, led us to re-examine the basis for endothelial cell responses to thrombin. Human umbilical vein endothelial cells (HUVEC) are known to express PAR1 and the trypsin/tryptase receptor, PAR2. Northern blots detected both of those receptors and, to a lesser extent, PAR3, but PAR4 message was undetectable and there was no response to PAR4 agonist peptides. To determine whether PAR3 or any other receptor contributes to thrombin signaling in HUVEC, PAR1 cleavage was blocked with two selective antibodies and PAR1 activation was inhibited with the antagonist, BMS200261. The antibodies completely inhibited HUVEC responses to thrombin, but BMS200261 was only partly effective, even though separate studies established that the antagonist completely inhibits PAR1 signaling at the concentrations used. Since peptides mimicking the PAR1 tethered ligand domain can also activate PAR2, we asked whether the remaining thrombin response in the presence of the antagonist could be due in part to the intermolecular transactivation of PAR2 by cleaved PAR1. Evidence that transactivation can occur was obtained in COS-7 cells co-expressing PAR2 and a variant of PAR1 that can be cleaved, but not signal. There was a substantial response to thrombin only in cells expressing both receptors. Conversely, in HUVEC, complete blockade of the thrombin response by the PAR1 antagonist occurred only when signaling through PAR2 was also blocked. From these observations we conclude that 1) PAR1 is the predominant thrombin receptor expressed in HUVEC and cleavage of PAR1 is required for endothelial cell responses to thrombin; 2) although PAR3 may be expressed, there is still no evidence that it mediates thrombin responses; 3) PAR4 is not expressed on HUVEC; and 4) transactivation of PAR2 by cleaved PAR1 can contribute to endothelial cell responses to thrombin, particularly when signaling through PAR1 is blocked. Such transactivation may limit the effectiveness of PAR1 antagonists, which compete with the tethered ligand domain rather than preventing PAR1 cleavage

    Training for team-based care: Development of a continuing education curriculum for general practice pharmacists in australia

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    © 2020 FIP. Background: The integration of pharmacists into primary care and general practice teams is expanding. Equipping pharmacists with the skills and knowledge to perform as part of a primary care team will facilitate this expanded scope of practice. Aim: This paper describes the rationale and approach for the development of a competency aligned curriculum of a postgraduate pharmacist education programme in Australia. Methods: The authors describe an evidence-based approach to curriculum development including establishing an educational programme advisory committee, consultation with an expert panel of pharmacy practice educators, and mapping of curriculum to both learning outcomes and competency standards. Conclusions: The curriculum design approach ensures the programme is designed to provide pharmacists with the skills, training and knowledge required to perform the General Practice pharmacist role. The education programme is due to be piloted in 2020, followed by an evaluation to allow further adjustment and improvement of the course design

    Framework to assess the quality of mHealth apps: a mixed-method international case study protocol

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    Introduction: Healthcare professionals (HCPs) often recommend their patients to use a specific mHealth app as part of health promotion, disease prevention and patient self-management. There has been a significant growth in the number of HCPs downloading and using mobile health (mHealth) apps. Most mHealth apps that are available in app stores employ a ‘star rating’ system. This is based on user feedback on an app, but is highly subjective. Thus, the identification of quality mHealth apps which are deemed fit for purpose can be a difficult task for HCPs. Currently, there is no unified, validated standard guidelines for assessment of mHealth apps for patient safety, which can be used by HCPs. The Modified Enlight Suite (MES) is a quality assessment framework designed to provide a means for HCPs to evaluate mHealth apps before they are recommended to patients. MES was adapted from the original Enlight Suite for international use through a Delphi method, followed by preliminary validation process among a population predominantly consisting of medical students. This study aims to evaluate the applicability and validity of the MES, by HCPs, in low, middle and high income country settings. Methods and analysis: MES will be evaluated through a mixed-method study, consisting of qualitative (focus group) and quantitative (survey instruments) research, in three target countries: Malaŵi (low income), South Africa (middle income) and Ireland (high income). The focus groups will be conducted through Microsoft Teams (Microsoft, Redmond, Washington, USA) and surveys will be conducted online using Qualtrics (Qualtrics International, Seattle, Washington, USA). Participants will be recruited through the help of national representatives in Malawi (Mzuzu University), South Africa (University of Fort Hare) and Ireland (University College Cork) by email invitation. Data analysis for the focus group will be by the means of thematic analysis. Data analysis for the survey will use descriptive statistics and use Cronbach alpha as an indicator of internal consistency of the MES. The construct validity of the mHealth app will be assessed by computing the confirmatory factor analysis using Amos. Ethics and dissemination: The study has received ethical approval from the Social Research Ethics Committee (SREC) SREC/SOM/03092021/1 at University College Cork, Ireland, Malaŵi Research Ethics Committee (MREC), Malaŵi MZUNIREC/DOR/21/59 and Inter-Faculty Research Ethics Committee (IFREC) of University of Fort Hare (REC-2 70 710-028-RA). The results of the study will be disseminated through the internet, peer-reviewed journals and conference presentations

    Decision-making Styles in a Real-Life Decision: Choosing a College Major

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    Undergraduate students were surveyed at the beginning stages of a potentially life-framing decision: choosing a college major. We investigated the relationships among individual difference variables (decision-making styles, planning proclivities, and epistemological orientations), cognitive measures of performance (e.g., amount of information gathered and considered); and affective reactions to, and descriptive ratings of, the decision-making process. There were few significant relationships between individual differences and performance measures. However, there were significant relationships found between individual differences measures and affective reactions to, or descriptive ratings of, the decision-making process. We suggest that stylistic measures have their effects in the way individuals frame the decision-making process rather than in the way they go about gathering or structuring information

    Applying Community-Based Participatory Research Partnership Principles to Public Health Practice-Based Research Networks

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    With real-world relevance and translatability as important goals, applied methodological approaches have arisen along the participatory continuum that value context and empower stakeholders to partner actively with academics throughout the research process. Community-based participatory research (CBPR) provides the gold standard for equitable, partnered research in traditional communities. Practice-based research networks (PBRNs) also have developed, coalescing communities of practice and of academics to identify, study, and answer practice-relevant questions. To optimize PBRN potential for expanding scientific knowledge, while bridging divides across knowledge production, dissemination, and implementation, we elucidate how PBRN partnerships can be strengthened by applying CBPR principles to build and maintain research collaboratives that empower practice partners. Examining the applicability of CBPR partnership principles to public health (PH) PBRNs, we conclude that PH-PBRNs can serve as authentic, sustainable CBPR partnerships, ensuring the co-production of new knowledge, while also improving and expanding the implementation and impact of research findings in real-world settings.ECU Open Access Publishing Support Fun

    The Family Name as Socio-Cultural Feature and Genetic Metaphor: From Concepts to Methods

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    A recent workshop entitled The Family Name as Socio-Cultural Feature and Genetic Metaphor: From Concepts to Methods was held in Paris in December 2010, sponsored by the French National Centre for Scientific Research (CNRS) and by the journal Human Biology. This workshop was intended to foster a debate on questions related to the family names and to compare different multidisciplinary approaches involving geneticists, historians, geographers, sociologists and social anthropologists. This collective paper presents a collection of selected communications
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